Generally, packed column chromatography systems separate analytes of a sample using a separation unit, such as a chromatographic column. For example, a sample containing various analytes, such as chemical compounds, or other sample constituents, dissolved in a solvent solution may be injected into a mobile phase fluid stream with an injection valve, where the mobile phase typically comprises one or more solvents. The sample-containing mobile phase flows through the chromatographic column which selectively retains the analytes from the sample. The analytes from the sample experience a differential retention with the column's stationary phase, e.g., using packing material or sorbent within the chromatographic column, and the relative elution strength of the mobile phase. The separated analytes may then be directed to a detector for detection and analysis, where each of the analytes emerges from the chromatographic column at a different time corresponding to the respective differential retention of that analytes within the chromatographic column. Detection over time results in “peaks” respectively corresponding to the analytes of the sample, where magnitude of each peak correlates to the amount of the corresponding analytes in the sample. In preparative chromatography systems, the separated sample constituents may be collected by various fraction collection devices.
Typically, the mobile phase is a mixture of solvents provided by corresponding pumping systems. The solvents include at least a strong solvent and a weak solvent referring to the solvents relative elution strength in relation to each other and to the stationary phase being used. The strong solvent favors a partitioning of the sample components into the mobile phase, thus lessening retention, or providing faster transiting of the chromatographic column. The weak solvent favors partitioning of the sample components on the column's stationary phase thus increasing retention, and may serve to moderate the effects of the strong solvent. Attempts are made to balance the mobile phase composition or ratio between the strong and weak solvents in order to provide an acceptable comprise between speed of the chromatography operation and quality of the analytical results.
One type of chromatography system is Supercritical Fluid Chromatography (SFC). SFC with packed columns typically uses an organic solvent termed a modifier, such as methanol, ethanol, propanol, etc., as the strong solvent and highly compressed dense gas, most commonly carbon dioxide (CO2), as the weak solvent. It can be noted that while the name of the technique, SFC, implies use of fluids in a supercritical state, the actual use includes fluids that while dense, are not necessarily supercritical.
Supercritical Fluid Extraction (SFE) is the process of separating one or more components (the extractants) from another (the matrix) using fluids similar to a SFC mobile phase as the extracting solvents. Extraction is usually from a solid matrix, but can also be from liquids. SFE can be used as a sample preparation step for analytical purposes, or on a larger scale to either strip unwanted material from a product or collect a desired product. Again, carbon dioxide (CO2) is the most used supercritical fluid, sometimes modified by co-solvents such as ethanol or methanol.
The properties of a supercritical fluid can be altered by varying the pressure and temperature, allowing selective extraction. A typical SFE system includes a pumping system for the CO2, and any co-solvents, a pressure cell to contain the sample, the ability to maintain pressure in the system and a collecting vessel or vessels. The liquid may be pumped to a heating zone, where its temperature may be raised to true supercritical conditions. It then passes into the extraction vessel, where it rapidly diffuses into the solid matrix and dissolves the material to be extracted. The dissolved material is swept from the extraction cell into a separator at lower pressure, and the extracted materials are removed.
Various sample collection approaches exist and are disclosed in the following documents: “Sample collection container, sample collection apparatus, and sample collection method in supercritical fluid system”, U.S. Pat. No. 8,327,725 to Kanamoto which is directed to a vial cap based system; “Apparatus and method for preparative supercritical fluid chromatography”, U.S. Pat. No. 6,413,428 to Berger which is directed to a pressurized tube collector; “Fractionation process for mixtures by elution chromatography with liquid in supercritical state and installation for its operation”, U.S. Pat. No. 4,478,720 to Perrut which is directed to high pressure cyclone collections; “Process Flowstream Collection System”, U.S. Pat. No. 8,262,760 to Fogelman which is directed to a near atmospheric separator; and “Collection system for purification flowstreams”, U.S. Publication No. 2014/0190890 to Sidhu which is directed to utilizing a specialized dripper within a pressurized separator. U.S. Publication No. 2014/0283688 to Fogleman et al. entitled “Self Cleaning Gas-Liquid Separator for Serial or Parallel Collection of Liquid Fractions” is directed to a porous coalescence filter used as part of a gas-liquid separator.
Many of these prior approaches generally contain the effluent of the separation under some modest, or in some cases, a controlled, pressure. After the separation in a containing vessel, the CO2 is generally removed from the opposite end of the liquid exit, or opposite the collected liquid pool. These conventional separators generally operate in either batch (chiral) mode, or sequential (library) mode. Batch mode operation often obviates the need for strong cleaning of the collector as the same compound is seen on each (one of many) collectors for avoidance of carryover. Sequential collectors need to generally exhibit a high degree of self-cleaning with minimum carry over or broadening of fluidic elements as each collection may immediately change to the next fraction/vessel. Further, successful collection of sequential fractions cut downstream of the separator may require a highly deterministic (in time) way of recognizing a fraction start and stop. Broadening of a peak within the separator prior to the fraction cut can cause adjacent peaks to merge resulting in loss of both purity and recovery of the collected fraction.
It is desirable to provide for the collection of fractions without requiring a contained vessel to separate the gaseous component, requiring external pressure control to reduce aerosol formation, or requiring specifically adapted collection vessels, while additionally allowing downstream fraction cuts.